Rapid and Efficient Generation of Regulatory T Cells to Commensal Antigens in the Periphery

Katherine Nutsch, Jiani N. Chai, Teresa L. Ai, Emilie Russler-Germain, Taylor Feehley, Cathryn R. Nagler, Chyi Song Hsieh

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82 Scopus citations


Commensal bacteria shape the colonic regulatory T (Treg) cell population required for intestinal tolerance. However, little is known about this process. Here, we use the transfer of naive commensal-reactive transgenic T cells expressing colonic Treg T cell receptors (TCRs) to study peripheral Treg (pTreg) cell development in normal hosts. We found that T cells were activated primarily in the distal mesenteric lymph node. Treg cell induction was rapid, generating >40% Foxp3+ cells 1 week after transfer. Contrary to prior reports, Foxp3+ cells underwent the most cell divisions, demonstrating that pTreg cell generation can be the dominant outcome from naive T cell activation. Moreover, Notch2-dependent, but not Batf3-dependent, dendritic cells were involved in Treg cell selection. Finally, neither deletion of the conserved nucleotide sequence 1 (CNS1) region in Foxp3 nor blockade of TGF-β (transforming growth factor-β)-receptor signaling completely abrogated Foxp3 induction. Thus, these data show that pTreg cell selection to commensal bacteria is rapid, is robust, and may be specified by TGF-β-independent signals.

Original languageEnglish
Pages (from-to)206-220
Number of pages15
JournalCell Reports
Issue number1
StatePublished - Sep 27 2016


  • CNS1 Foxp3
  • Notch2-dependent dendritic cells
  • TGFβ
  • commensal microbiota
  • pTreg
  • peripheral regulatory T cells


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